In the study, the brentuximab vedotin regimen reduced the risk of progression, death, or initiation of new therapy by 23% compared with ABVD. The 2-year modified PFS rate was 82.1% with brentuximab vedotin compared with 77.25% for standard chemotherapy (HR, 0.77; 95% CI, 0.60-0.98; P = .035). Among patients with stage IV disease, the use of brentuximab vedotin resulted in a 29% reduction in the risk of progression, death, or need for new therapy (HR, 0.71; P = .023).

Brentuximab vedotin can now be marketed for this indication in the 28 member states of the European Union, as well as Norway, Liechtenstein, and Iceland.

"The decision by the European Commission is a welcomed advancement for patients with previously untreated stage IV Hodgkin lymphoma—a population that has not been offered a new treatment option in decades," Anna Sureda, MD, PhD, head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d'Oncologia – Hospital Duran i Reynals, said in a statement.

"Patients with stage IV disease carry a higher risk of progression following their first therapy and experience poorer outcomes as a result. The approval of this regimen may help address this unmet need by providing European physicians and their patients with a new option that showed significant benefit compared to ABVD along with a safety profile consistent with when Adcetris is used as a single agent," added Sureda.

The phase III ECHELON-1 trial enrolled 1334 patients with stage III/IV classical Hodgkin lymphoma. All patients had not received prior treatment with systemic chemotherapy or radiotherapy and had an ECOG performance status of ≤2. Patients ranged in age from 18 to 83, the median age was 36 years, and 58% were men.

In both arms, treatment was given on days 1 and 15 of a 28-day cycle. Doxorubicin was given at 25 mg/m2, vinblastine was administered at 6 mg/m2, and patients received dacarbazine at 375 mg/m2. In the investigational arm, brentuximab vedotin was administered at 1.2 mg/kg and in the control group bleomycin was administered at 10 units/m2.

The primary endpoint of the study was modified PFS by independent review committee. Under the modified criteria, PFS was defined as time to progression, death, or receipt of additional therapy for those not in complete response (CR). The modified endpoint was meant to eliminate the potential impact of consolidation treatment with chemotherapy or radiotherapy. Secondary endpoints included overall survival and safety.

PFS was met with 117 events in the brentuximab vedotin arm and 146 events in the AVBD arm. At a median follow-up of 24.9 months, the 2 year modified PFS was 82.1% (95% CI, 78.7-85.0) with the brentuximab vedotin regimen compared with 77.2% (95% CI, 73.7-80.4) with ABVD.

The CR rate was 73% for the brentuximab vedotin arm and 70% for the ABVD arm. In addition, researchers found that 33% fewer patients treated with the brentuximab vedotin regimen received subsequent chemotherapy or high-dose chemotherapy and transplant compared with the patients treated with ABVD.

Safety profiles were consistent with known toxicities of the single agents. Grade ≥3 infections were more common in the brentuximab vedotin group (18%) than the ABVD arm (10%).

Neutropenia was reported in 58% of patients who received the brentuximab vedotin regimen compared with 45% who received ABVD. In the brentuximab vedotin arm, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with GCSF than among those who did not (11% vs 21%).

There were 28 deaths in the brentuximab vedotin cohort and 39 in the ABVD arm (HR for interim overall survival, 0.72; 95% CI, 0.44-1.17; P = 0.19). Among the deaths that occurred during treatment, 7 of 9 in the brentuximab vedotin group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.

According to the co-developers of brentuximab vedotin, Takeda Pharmaceutical Company and Seattle Genetics, the CD30-targeted antibody-drug conjugate previously had approved EU indications for the treatment of adult patients with relapsed/refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option; adult patients with relapsed or refractory systemic anaplastic large cell lymphoma; adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT; and adult patients with CD30-positive cutaneous T-cell lymphoma after at least 1 prior systemic therapy.